The synthesis of specific inhibitors of the uptake of the biogenic amines, norepinephrine, dopamine and 5-hydroxytryptamine in the central nervous system is proposed. The compounds will be used in studies on the role of neuronal uptake in psychotropic drug action and in studies examining the properties of the carrier system. The carrier system will be examined in vitro with purified brain homogenates and nerve ending particles or synaptosomes, and in vivo with conventional pharmacological procedures. The compounds to be synthesized are based on amphetamine which has been shown to be a potent inhibitor of the uptake system. The basic amphetamine structure will be modified by increasing lipophilicity and bulk to enhance specificity. In addition, reactive functional groups will be introduced to prepare irreversible inhibitors. These irreversible inhibitors will be used as active site labelling devices to quantitate and characterize the uptake system.